Flow detection apparatus and method

ABSTRACT

Fluid sample tester assembly (12) comprises a cartridge (6) having a pressure chamber (22) and entrance port (20) connected by a passageway (24). An analyte reagent (36) is positioned along the fluid passageway so that when a liquid sample (28) is drawn through the entrance port into the passageway, the analyte reagent mixes with the sample. The sample is preferably drawn into the cartridge by temporarily reducing the volume of the pressure chamber, applying the sample to the entrance port and then returning the pressure chamber to its initial volume; this can also be done by heating the chamber, contacting the sample and then cooling the chamber. The end of the sample defines a boundary surface (30) along the fluid passageway. Positive and negative pressure is applied to the sample to cause the boundary surface to oscillate within the passageway. The position of the boundary surface is continuously monitored so that continuous boundary position data is obtained and is analyzed to obtain a flow-related characteristic, typically speed of coagulation, of the sample.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of and claims the benefit of U.S.application Ser. No. 08/579,367, filed Dec. 27, 1995, now U.S. Pat. No.5,736,404, the disclosure of which is incorporated by reference.

This is related to U.S. patent application Ser. No. 08/269,253 filedJun. 30, 1994 and entitled Sample Collection and Manipulation Apparatusand Method, now U.S. Pat No. 5,700,695, the disclosure of which isincorporated by reference.

BACKGROUND OF THE INVENTION

Flow-related characteristics of a fluid, such as changes in viscositywith temperature of a liquid, are often measured to provide importantinformation about the fluid. The speed at which blood coagulates whensubjected to a coagulation reagent has particular utility in the medicalfield. Numerous methods have been proposed and used to measurecoagulation. Some of the methods are suitable for use using disposablecuvettes or strips. For example, U.S. Pat. No. 4,797,369 to Mintzteaches a mechanical method to detect clot formation by looking forfibrin threads as a probe is pulled from a sample/reagent mixture. Othermethods use magnetic stir bars or particles that are located in thesample/reagent mixture, under the influence of an oscillating magneticfield, looking for a reduction in movement as the clot forms and gelsthe sample. See, for example, U.S. Pat. No. 4,849,340 to Oberhardt.Another method, shown in U.S. Pat. No. 4,756,884 to Hillman, disclosemonitoring the capillary flow of a whole blood sample by observing anon-stationary speckle pattern when coherent light is scattered from thecells in the moving sample; coagulation is detected when the specklepattern becomes stationary, indicating the cessation of sample flow inthe capillary.

Air pressure has been used to move samples in a cuvette for the purposeof measuring coagulation time. For example, U.S. Pat. No. 4,725,554 toSchildknecht uses air pressure to move the sample back and forth acrossan edge to create a clot, and then detects the formation of the clot atthe edge by measuring a change in optical absorption. Other examples areshown in U.S. Pat. Nos. 3,890,098 to Moreno and 3,486,859 to Greinerwhere two cups or chambers are interconnected through a capillary, andair pressure is used to transfer the liquid reagent and samplecombination back and forth until a clot blocks the capillary and theincrease in air back pressure is detected.

U.S. Pat. No. 5,302,348 to Cusack discloses a coagulation measurementapparatus which uses disposable cuvette, one end of which is insertedinto the measurement apparatus. The cuvette includes a cup-shaped samplereservoir and a pair of open-ended passageways. Each passageway opens tothe ambient environment through the sample reservoir at their proximalends and to the ambient environment at their spaced-apart distal ends. Asample drop of blood is placed in the fluid reservoir positionedexternal of the apparatus. The open distal end of one of the passagewaysis connected to a first pump which draws a fluid sample into the firstpassageway. A second pump is connected to the open distal end of thesecond passageway and draws an unused portion of the sample into thesecond passageway so that no sample is left in the sample receptacle.The test sample in the first passageway is caused to oscillate back andforth through a restricted area which is preferably treated to be a moreefficient clotting surface. A pair of light sensors, one on each side ofthe restricted area, are used to determine when the leading or trailingedge of the test sample passes a sensor. Endpoint, that is whensufficient clotting has occurred, is determined when the time for thesample to traverse the restricted region is a predetermined percentagelonger than an immediately proceeding time. The rate of oscillation canbe adjusted throughout a run to avoid breaking apart a weak clot with along clotting time. A heater is located under the cuvette when insertedinto the measurement apparatus to set the operating temperature for theparticular chemical reaction.

SUMMARY OF THE INVENTION

The present invention is directed to a fluid detection apparatus andmethod by which a fluid sample tester can be made to be simpler inconstruction than prior art systems and can provide continuousinformation about the flow characteristic being measured using adisposable cartridge. The cartridge is simpler in construction and moresafely disposed of than conventional cartridges.

The cartridge defines a pressure chamber, an entrance port and apassageway fluidly coupling the two. An analyte reagent is preferablypositioned along the fluid passageway so that when a fluid sample isdrawn through the entrance port into the passageway, the analyte reagentmixes with the fluid sample. The ends of the fluid sample defineboundary surfaces positioned along the fluid passageway. Pressure isapplied to the fluid sample to move at least one of the boundarysurfaces along the passageway. The position of the boundary surface iscontinuously monitored so that continuous boundary position data isobtained. The boundary position data is analyzed to obtain aflow-related characteristic of the fluid sample. For example, speed ofcoagulation of a blood sample can be measured in this way. Preferably,positive and negative pressures are applied to the fluid sample so thatthe boundary surface oscillates along the passageway as the boundaryposition data is obtained.

The sample can be drawn into the passageway by temporarily reducing thevolume of the pressure chamber, applying the test sample to the entranceport and then returning the volume of the pressure chamber to itsoriginal volume. Another method to draw in the sample would be to drawout a portion of the gas in the pressure chamber using, for example, asyringe having a needle cannula passing through an elastomeric septum inthe wall of the pressure chamber.

The fluid sample, typically a liquid, can also be drawn into thecartridge by first heating the pressure chamber with the entrance portopen to the ambient environment to reduce the density of the gas withinthe pressure chamber. The fluid sample is then applied to the entranceport. As the gas in the pressure chamber cools, the liquid sample isdrawn into the passageway due the partial vacuum created in the pressurechamber.

One of the primary advantages of the invention is its simplicity. Nofluid pumps, as are used with, for example, the Cusack apparatus, areneeded. Preferably, the test sample is drawn into the cartridge bymechanically reducing the volume of the pressure chamber. Alternatively,the sample can be drawn into the cartridge by cooling the gas in thepressure chamber. Assuming cooling is brought about after first heatingabove ambient temperature, this provides an additional advantage upondisposal of the cuvette. That is, once a cartridge returns to ambienttemperature (and once the sample is drawn into the pressure chamber bymechanically reducing the volume of the pressure chamber), the sample iseffectively locked within the passageway in the cartridge since there ispreferably only one opening from the ambient environment to thepassageway. Thus, unlike the cuvette shown in Cusack which has openingson each end of each of its passageways, the liquid sample within thecartridge is effectively prevented from leaking out upon disposal.

A further advantage of the invention is that the amount of fluidmovement necessary can be made very small if needed. For example, somecoagulation assays produce a relatively fragile clot that can be easilydisrupted by excessive fluid movements. With the present invention,endpoint detection with only a very small amount of fluid displacementwill work with only a very small signal in the detector. This isachieved by continuously obtaining positional data and appropriatemathematical manipulation of data. In contrast, the system shown inCusack requires enough movement to commutate between the physicallimitations of the two detectors.

With the present invention the oscillatory movement of the sample withinthe fluid passageway is preferably accomplished by deflection of a wallof the pressure chamber. This can be accomplished in several differentways. For example, various types of solenoid drivers can be used todeflect and release one wall of the pressure chamber. Electromagneticdrivers or even bending of the pressure chamber can be used as well. Thesame structure used to oscillate the sample can also be used toinitially reduce the volume of the pressure chamber to draw the sampleinto the passageway. Oscillating pressures can also be created bythermal means, that is, raising and lowering the temperature of thepressure chamber. This would be useful when the frequency of movement isnot needed to be that quick.

Since the pressure chamber is sealed, no specialized pressure couplingsare needed between the disposable cartridge and the tester. By keepingthe entrance port of the cartridge external of the tester, the portionof the cartridge which enters the tester is completely sealed; thishelps to reduce the possibility of bio-contamination of the tester fromthe sample or its aerosol components which, in the apparatus disclosedin the Cusack patent, pass into the tester.

Another advantage of the invention is that a disposable cartridge can bemade using a very simple, inexpensive construction technique such aslamination or blow molding techniques. Precision, fluid-tight fittingsare not necessary, in contrast with the cuvette of the Cusack patent.

Other features and advantages of the invention will appear from thepreferred embodiment which has been set forth in detail in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overall view showing a fluid sample tester assembly,including a fluid sample tester and a cartridge, made according to theinvention;

FIG. 2 is an exploded view showing the cartridge of FIG. 1 prior toassembly;

FIG. 3 schematically illustrates heating of the pressure chamber definedwithin the cartridge of FIG. 2 after the cartridge has been insertedinto a tester of FIG. 1;

FIG. 4 schematically represents cooling the pressure chamber of thecartridge of FIG. 3 using a fan within the tester of FIG. 1 to draw thetest sample from the entrance port into the passageway;

FIG. 5 is a simplified representation of the cartridge of FIG. 4suggesting the positioning of a light source and a photodetector aboveone of the boundary surfaces of the liquid sample within the passagewayand a solenoid driver causing a portion of the cartridge bounding thepressure chamber to flex back and forth, thus decreasing and increasingthe volume of the pressure chamber, causing the boundary surface of theliquid sample to oscillate between the photodetector and light source;

FIGS. 5A and 5B are enlarged, simplified top and side views illustratingthe relative positions of the photodetector, light source and theboundary surface of the liquid sample within the passageway of FIG. 5;

FIG. 6 illustrates an alternative solenoid driver used to deflect onewall of the pressure chamber using a linear motion generally parallel tothe pressure chamber;

FIG. 7 illustrates a motor driver having a rotating cam used to deflectthe wall of the pressure chamber in an oscillating manner;

FIGS. 8 and 9 illustrate two different electromagnetic schemes fordeflecting a wall of the pressure chamber to create the oscillation ofthe boundary surface of the liquid sample;

FIG. 10 illustrates a cartridge similar to the cartridge of FIG. 4 butincluding pairs of entrance ports, pressure chambers and connectingpassageways, in which the oscillating change in volume of the pressurechambers is achieved by deflection and release of one end of thecartridge so that the cartridge flexes about an axis passing through thepressure chambers, thereby increasing and decreasing the volumes of thepressure chambers to create the desired oscillatory movement of theboundary surfaces of the liquid samples;

FIG. 11 illustrates a further embodiment of the cartridge of FIG. 1 inwhich the pressure chamber has been divided into larger and smaller,interconnected pressure chambers in which both the pressure chambers areused to draw the liquid sample into the passageway and the smallerpressure chamber is used to create the oscillatory motion for theboundary surface of the liquid sample within the passageway when verysmall oscillations are desired; and

FIG. 12 illustrates a further embodiment of the cartridge of FIG. 1 inwhich a waste channel is formed off of the passageway coupled to asecondary pressure chamber used to draw off excess fluid sample from thepassageway and entrance port.

DESCRIPTION OF THE PREFERRED EMBODIMENT

FIG. 1 illustrates a fluid sample tester assembly 2 made according tothe invention. Assembly 2 includes a fluid sample tester 4 and acartridge 6. Cartridge 6 is typically disposable after use. Cartridge 6can be made by any number of methods. One such method is suggested inFIG. 2 in which cartridge 6 comprises a top 8, a bottom 10 and a base 12sandwiched between the top and bottom. Base 12 has an enlarged openregion defining a pressure chamber interior 14, a relatively narrowpassageway groove 16 terminating at pressure chamber interior 14 at oneend and an enlarged end 18 at the other. Enlarged end 18 of passagewaygroove 16 is aligned with an entrance port 20 formed in top 8. Top 8,bottom 10 and base 12 can be made of any number of materials, such aspolycarbonate, ABS or polystyrene, and are preferably secured to oneanother to create cartridge 6 through the use of adhesives, ultrasonicwelding techniques, thermal bonding, etc. Instead of having entrance 20preformed into top 8, entrance port 20 could be formed after assembly oftop 8, bottom 10 and base 12. Once assembled, top 8, bottom 10 and base12 define a pressure chamber 22 connected to entrance port 20 by apassageway 24.

In an embodiment designed to test coagulation of whole blood, base 12 is0.25 mm (0.010 in.) thick, pressure chamber 22 has a volume of about0.05 ml (0.003 in³) and passageway 24 has a cross-sectional area ofabout 0.25 mm² (0.0004 in²) and a length of about 25 mm (1 in). Entranceport 20 has a volume of about 0.020 ml (0.0012 in³) from the opening 20formed in top 8 and enlarged end 18 formed in base 12.

After placement of cartridge 6 through an entrance opening 25 in fluidsample tester 4, pressure chamber 22 can be heated in preparation forapplying a fluid sample to entrance port 20. This is done to reduce thedensity of gas within pressure chamber 22 so that pressure chamber 22acts as a thermal pressure chamber. To aid heating the gas, typicallyair, within pressure chamber 22 the surface of bottom 10 or top 8bounding pressure chamber interior 14 is treated with, for example,carbon to create a radiation absorption surface. When placed withinfluid sample tester 4, pressure chamber 22 is automatically aligned witha radiation source 26 within tester 4. Radiation source 26 is thenenergized for a period of time sufficient to properly heat the interiorof pressure chamber 22. Other methods for heating the interior ofpressure chamber 22, such as through the use of direct contact heatersor flowing heated air across cartridge 6, could be used as well. Heatingcould also occur external of tester 4.

After pressure chamber 22 is properly heated, an appropriate sample isapplied to entrance port 20. This can be done automatically or manually,such as through the use of an eyedropper or a pipette. In a manual mode,cartridge 6, when properly positioned within tester 4, has a portion ofcartridge 6 external of fluid sample tester 4 to permit user access toentrance port 20. To draw the fluid sample 28 into passageway 24, thegas within pressure chamber 22 is cooled. This can be accomplishedsimply by permitting the thermal mass of cartridge 6 to cool the gaswithin pressure chamber 22 or, as suggested by FIG. 4, a fan 30 can beused to blow cool air across cartridge 6 to help cool pressure chamber22. Other ways of cooling pressure chamber 22, such as by the use ofdirect-contact Peltier heaters/coolers, can be used as well.

FIGS. 5-5B illustrate, in simplified form, the monitoring andmanipulation of fluid sample 28 by fluid sample tester 4. Fluid sample28 has a boundary surface 30 at either end. Sample 28 is positionedwithin passageway 24 so that the boundary surface 30 closest to pressurechamber 22 lies positioned between a photodetector 32, preferably aphotodiode, and a light source 34, commonly an LED. Photodetector 32 andlight source 34 are connected to an analyzer 35 used to measure, in thepreferred embodiment, coagulation times for blood samples as theflow-related characteristic. To this end a coagulation reagent 36, seeFIG. 2, such as thromboplastin, is applied to bottom 10 of cartridge 6at a position aligned with passageway groove 16 so that fluid sample 28will come in contact with and mix with reagent 36 upon being drawn intopassageway 24.

In the preferred embodiment, at least top 8 and bottom 10 aretransparent or translucent so that the amount of light detected byphotodetector 32 depends upon the position of boundary surface 30. Theinitial position of boundary surface 30 is dependent on the change intemperature in, and thus the density of, the gas within pressure chamber22. Once the temperature within pressure chamber 22 has stabilized forthe period of the test, it is desired to cause boundary surface 32 tooscillate within the region of detection between photodetector 32 andlight source 34. Since photodetector 32 continuously monitors theposition of boundary surface 30, this permits analyzer 35 to obtaincontinuous boundary position data regarding the boundary surface 30.

To create this oscillatory movement of boundary surface 30, the pressurewithin pressure chamber 22 is changed. This can be done thermally byheating and cooling the gas within pressure chamber 22. However, heatingand cooling cycle times are limited to about 1 Hz. In the preferredembodiment of FIG. 5 a solenoid driver 40 is used to mechanically flexor deflect that portion of top 8 overlying pressure chamber interior 14.Solenoid driver 40 includes a solenoid 42 which causes a solenoid shaft44 to reciprocate. Solenoid shaft 44 presses against top 8 causing top 8to deflect inwardly, thus reducing the volume of pressure chamber 22. Onthe reverse movement of solenoid shaft 44 away from pressure chamber 22,the resilience of top 8 causes top 8 to deflect back to its originalposition, thus enlarging pressure chamber 22 back to its original volumeto cause boundary surface 30 to move back to its original position. Inone embodiment, this movement in the direction of arrow 46 is about 0.25mm (0.010 in) at a frequency of about 50 Hz. In this embodiment,passageway 24 is about 25 mm long having a cross-sectional area of about25 mm². The total volume of sample 28 is about 5 mm³ (0.0003 in³) andthus occupies about 80% of passageway 24. The cycle speed of solenoiddriver 40 and the amount of travel of solenoid shaft 44, whichdetermines the distance boundary surface 30 moves in the direction ofarrow 46, can change depending upon the particular test conducted andthe properties of the sample being tested. For example, some coagulationassays produce a more fragile clot that can be easily disrupted byexcessive fluid movement. The invention permits detection of boundarysurface 30 quite accurately with only a very small amount of fluiddisplacement. This is not possible with conventional systems in whichthe boundary surface must pass to discretely positioned points for anyinput data to be obtained. This aspect of the present invention permitsthe present invention to be easily adjusted to accommodate theparticular coagulation assay.

FIG. 6 illustrates an alternative embodiment of the invention in which asolenoid driver 48 has a bent shaft 50 driven by a solenoid 52. Thelinear movement of bent shaft 50 in the direction arrow 54 causesdeflection of top 8 of cartridge 6 causing boundary surface 30 tooscillate back and forth along the direction of arrow 56.

FIG. 7 illustrates a motor driver 58, including a motor 60 and arotating shaft 62. Shaft 62 has a cam lobe 64 at its end so thatrotation of shaft 62 causes cam lobe 64 to alternatingly depress andrelease top 8 of cartridge 6 to create the desired oscillatory movementof boundary surface 30 of sample 28. Driver 58 provides a frequencyrange of about 0.1 to as high as the motor RPM if required.

FIGS. 8 and 9 disclose electromagnetic means for deflecting top 8 orbottom 10 of cartridge 6. Electromagnetic driver 66 of FIG. 8 includesan electromagnet 68 on one side of pressure chamber 22 and aspring-loaded metal shoe 70 on the other side. Alternating currentflowing through electromagnet 68 alternatingly pulls and releases metalshoe 70 towards and away from it causing the metal shoe to alternatinglydeflect and release bottom 10 of cartridge 6. In FIG. 9 an electromagnet72 is used to deflect a magnet 74 towards and away from bottom 10 ofcartridge 6 to create the desired oscillatory movement for boundarysurface 30.

FIG. 10 illustrates a further embodiment of the invention in which acartridge 76 has pairs of pressure chambers 22, passageways 24 andentrance ports 20. This could be used when, for example, it is desiredto run two different samples at the same time or run a test sample and astandard sample for comparison. The embodiment of FIG. 10 is alsodifferent in that the oscillatory movement of boundary surfaces 30 areachieved by applying a bending force to cartridge 76 as indicated byarrow 78 for flexing the cartridge about a bend axis 80. This bendingmotion, illustrated in an exaggerated form by the end of cartridge 76 indashed lines, causes a change in the volumes of pressure chambers 22.

In some cases, it may be desired to draw in the sample using pressurechamber 22 as a thermal pressure chamber but the amount of movement ofboundary surface 30 is desired to be kept small because of, for example,fragile coagulation bonds. FIG. 11 illustrates a cartridge 84 defining apressure chamber 86 including a main region 88 and auxiliary region 90.Auxiliary region 90 is smaller so that when, for example, solenoid shaft42 of FIG. 5 is used to deflect that portion of the top of cartridge 84it deflects only that portion overlying subsidiary region 90. Thiscreates a much smaller change in volume for the pressure chamber 86 asopposed to pressure chamber 22 of cartridge 6. By positioning subsidiaryregion 90 at the position of solenoid shaft 44 used with cartridge 2, nochanges need be made to the position or actuation of solenoid driver 40of fluid sample tester 4 to achieve the reduced movement of boundarysurface 30.

In some situations, it may be necessary to very accurately meter theamount fluid sample within passageway 24. FIG. 12 illustrates acartridge 92 having a single entrance port 20, a passageway 24 and apair of pressure chambers 22, 22A. Pressure chamber 22A is coupled topassageway 24 at position 94 by a waste channel 96. In this case, thesample to be measured is drawn into passageway 24 until the samplereaches position 98. The remainder of the sample is then drawn intowaste channel 96 to leave a known quantity of sample 24 betweenpositions 94, 98 and completely evacuating any of the sample fromentrance port 20 and along passageway 24 between the entrance port andposition 94. Fluid sample 28 is then moved into the region of passageway24 so that boundary surface 30 is positioned between photodetector 32and light source 34. While the embodiment of FIG. 12 may be useful insome situations, it is not believed that such a precise metering of thefluid sample within passageway 24 will typically be necessary.

In use, cartridge 6 is inserted into fluid sample tester 4 throughentrance opening 25. Pressure chamber 22 is then heated for a desiredtime period. When the maximum temperature within pressure chamber 22 hasbeen reached, or slightly thereafter, fluid sample 28 is applied toentrance port 20. Fluid sample 28 is typically a sample of about 5-10 μlof whole blood. Fluid sample tester 4 is then activated to cool thepressure chamber 20 to draw the entire fluid sample 28 into passageway24. This causes sample 28 to come in contact with reagent 36 andprovides adequate mixing between the two. Contact of the sample with thecoagulation reagent initiates the start-time for the testing. Boundarysurface 30 of fluid sample 28 is, if necessary, moved to place itbetween photodetector 32 and light source 34. The solenoid driver 40 isthen actuated to cause solenoid 44 to reciprocate raising and loweringthe pressure within pressure chamber 22, thus, causing boundary surface30 to oscillate in the direction of arrow 46 while it lies betweenphotodetector 32 and light source 34.

Analyzer 35 continuously monitors the location of boundary surface 30 bycontinuously obtaining boundary condition information from photodetector32 as well as information regarding change in pressure within pressurechamber 22 due to the actuation of solenoid driver 40. This permits theanalyzer 35 to not only measure the magnitude of the signal fromphotodetector 32, which correlates with the position of boundary surface30, but also the phase of that signal relative to the driving pressurewithin pressure chamber 22 created by solenoid driver 40. The initialinformation obtained is used as baseline information prior tocoagulation, that is before the coagulating reagent has had a chance tobegin causing the whole blood sample to coagulate. The magnitude andphase of the detected optical signal from photodetector 32 is monitoreduntil a significant change is observed. A significant change in theboundary indicates that the whole blood sample has coagulated so that anend point time is obtained.

Coagulation time can be determined by visually monitoring the output 100from fluid sample tester 4. The output could, as shown in FIG. 1, beprinted on a paper strip 102 or viewed on a screen 104. The data canalso be stored on some type of magnetic media through a connection to acomputer, not shown. Also, tester 4 could be made so that only rawinformation from photodetector 32, light source 34 and solenoid driver40 is created and that raw data is then fed to a specially programmedcomputer which would perform the desired calculations and display andsave the test data in any desired format.

Various algorithms can be used to efficiently and automaticallydetermine the coagulation end point and resulting clotting time.

The above mechanical structure for oscillating the sample is preferablyused to initially draw the sample into passageway 24 instead of usingthe thermal process discussed above. By initially exhausting a largervolume of air from chamber 22 than occurs during the oscillatingmovement of solenoid shaft 44, an appropriate volume of sample 28 can bedrawn into passageway 24. Using mechanical means instead of thermalmeans to draw the sample into the passageway can result in a simplerapparatus and a simpler method of use than when the sample is initiallydrawn in using thermal means and oscillated using mechanical means.

Other modifications and variations can be made to disclose embodimentswithout departing from the subject of the invention as defined in thefollowing claims. For example, one or more of the boundaries of pressurechamber 22 could be made of an elastomeric material rather than aflexible, resilient plastic material as in the preferred embodiments.This could be especially useful when it is desired to draw sample 28into passageway 24 using mechanical means rather than treating pressurechamber 22 as a thermal pressure chamber. Instead of using an opticalsensor, such as photodetector 32, other types of sensors, such as acapacitance sensor, a conductance sensor, or an acoustic sensor, couldbe used.

What is claimed is:
 1. A system comprising:a cartridge comprising a basehaving a fluid passageway, a pressure chamber connected to one end ofthe fluid passageway, and a sample port at another end of thepassageway; and a fluid sample tester comprising: means for inducingpressure changes in the pressure chamber of the cartridge, whereinsample applied through the sample port will enter the passageway andwill be translated within the passageway by pressure changes in thepressure chamber; and means for continuously monitoring the boundarylayer positioning within the passageway wherein the position of aboundary of the sample within the passageway may be continuouslymonitored over time.
 2. The system according to claim 1 wherein thepressure change inducing means comprises means for cooling said pressurechamber.
 3. The system according to claim 1 wherein the pressure changeinducing means comprises means for cooling said pressure chamber.
 4. Thesystem according to claim 1 wherein the pressure change inducing meanscomprises means for heating and then cooling said pressure chamber. 5.The system according to claim 1 wherein the pressure change inducingmeans includes means for applying positive and negative pressure to thefluid sample so the boundary surface oscillates along the passageway. 6.The system according to claim 5 wherein the positive and negativepressure applying means comprises means for changing the volume of thepressure chamber.
 7. The system according to claim 5 wherein thepressure chamber is defined in part by a resilient, flexible wall andthe positive and negative pressure applying means comprises means fordeflecting and releasing said wall.
 8. The system according to claim 1wherein a portion of the cartridge defining the passageway is capable ofpassing light therethrough and the continuous monitoring means includesa photodetector.
 9. The system according to claim 8 wherein thephotodetector is positioned transverse to the passageway where thecartridge is in the fluid sample tester.
 10. The system according toclaim 1 further comprising an analyzer is adapted to obtain coagulationcharacteristic of a blood fluid sample.